The objective is to identify and characterize the humoral agent or system that maintains the elevated blood pressure in chronic one-kidney hypertension. We have shown that the blood pressure of rabbits with this form of hypertension can be lowered to normal by immunization with hog kidney extracts. The blood pressure-lowering antigen (antigen M) acts by eliciting the formation of an antibody which cross-reacts with and neutralizes an unknown factor in the rabbit that is essential for the maintenance of an elevated blood pressure. This unknown rabbit factor must be similar if not identical to antigen M. We have been working toward the isolation of antigen M and the cross-reacting rabbit factor in order that we might learn their nature and function. In order to facilitate this work, we have fused spleen cells from mice immunized with antigen M with mouse myeloma cells and have found hybrid cell lines that secrete an antibody to antigen M. The purified antibody lowers the blood pressure of one-kidney hypertensive rabbits to normal. It must therefore cross-react with the essential rabbit factor. We will use affinity chromtograhy on columns of immobilized monoclonal antibody to isolate antigen M and the essential rabbit factor. We will determine the chemical nature of both substances. We will also use labeled monoclonal antibody to locate the rabbit factor in kidney and other tissues. Further studies with purified rabbit factor will enable us to determine its function. We believe that this will lead us to our objective, which is to identify and characterize the pressor system that is responsible for the elevation of blood pressure in one-kidney hypertension.